What lessons for clinical practice can be learned from systematic reviews of animal studies? The case of anesthetic neurotoxicity

Animal research, as a means to advance biological and medical knowledge, dates back to Aristotle and Galen. A millennium and a half later, in 1865, Claude Bernard established blinded experiments in animals as a standard scientific method, including for toxicological research. However, using animals to advance human medicine has always been controversial and has recently come under renewed scrutiny to better inform future research and to reduce the large number of animals used in preclinical studies [1]. Part of this movement to evaluate animal experiments has been a dramatic increase in the number of systematic reviews and meta-analyses of animal studies, in order to assess the animal studies’ quality and their applicability to humans.

Anesthetic neurotoxicity, the immediate brain structural abnormalities observed following prolonged anesthetic exposure in numerous animal studies as well as long-term cognitive impairment found in several animal models, including nonhuman primates, have raised substantial concerns for human anesthesia practice. The evidence in human epidemiological studies has been more tempered, however, with several studies detecting abnormalities in academic performance, language development, or cognition, especially following repeated exposures, while other investigations, including a recent analysis of secondary outcomes of a randomized controlled trial, were unable to confirm neurological abnormalities following anesthetic exposure early in life [2].